Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How?

Four years after she nearly died from rabies, Jeanna Giese is being heralded as the first person known to have survived the virus without receiving a preventative vaccine. But Giese (pronounced Gee-See) says she would gladly share that honor with others if only doctors could show that the treatment used to save her could spare other victims as well. "They shouldn't stop 'till it's perfected," said Giese, now 19, during a recent interview about physicians' quest to refine the technique that may have kept her alive.

Giese's wish may come true. Another young girl infected with rabies is still alive more than a month after doctors induced a coma to put her symptoms on hold, just as they did with Giese. Yolanda Caicedo, an infectious disease specialist at Hospital Universitario del Valle in Cali, Colombia, who is treating the latest survivor, confirmed reports in the Colombian newspaper El País that the victim is an eight-year-old girl who came down with symptoms in August, about a month after she was bitten by an apparently rabid cat. Caicedo said that the family had sought treatment for the bite in Bolivar, at a hospital about three hours by foot from their rural home, but that the child, Nelsy Gomez, did not receive the series of vaccines that can prevent the virus from turning into full-blown rabies.

The five shots contain minute amounts of the dead rabies virus and are designed to nudge the body into developing antibodies to fight it. Patients are also given a shot of immunoglobulin (in this case a synthesized rabies antibody) to protect them while their immune systems produce antibodies to the vaccine virus. But the combination is only effective within six days of infection, before symptoms show up; when Gomez developed signs of the disease, it was too late for the shots. With no other options available, doctors induced a coma.

Caicedo is hopeful, but indicated that Gomez will face a long, slow recovery. She would not say how long Gomez was comatose but told ScientificAmerican.com that she had been awake for "a few days" and is stable. The child can move her fingers but cannot walk or eat on her own, and her eyes are open but she cannot speak yet and physicians are not sure if she can see, Caicedo says.

Giese, informed of the case, says that she "hopes and prays" that Gomez will survive.

Giese was the keynote speaker at a conference last week in Atlanta, where scientists gathered to discuss the latest research being conducted on ways to battle the deadly disease. During her talk, she urged physicians to continue efforts to pin down treatments that work.

Her parents cleaned the superficial wound and she says they did not believe it was necessary to seek further medical treatment. "We never thought of rabies," she says. By the time Giese began displaying signs of rabies three weeks later—fatigue, double vision, vomiting and tingling in her left arm—it was too late for the antirabies vaccine cocktail.

Instead of giving her up for dead, the doctors decided to "shut the brain down and wait for the cavalry to come" by inducing a coma to give her own immune system time to build up antibodies against the virus, says Rodney Willoughby, an infectious disease specialist who treated Giese at the Children's Hospital of Wisconsin in Milwaukee. Willoughby devised the treatment credited with saving Giese there, which has since become known as the Milwaukee protocol.

Rabies kills by compromising the brain's ability to regulate breathing, salivation and heartbeat; ultimately, victims drown in their own spit or blood, or cannot breathe because of muscle spasms in their diaphragms. One fifth die from fatal heart arrhythmia. Doctors believed that Giese might survive if they suppressed her brain function by sedating her while her immune system attacked the rabies virus.

This was the first time the therapy was attempted, and doctors had no clue if it would work or, if it did, whether it would leave her brain damaged. But Willoughby says it was the only chance doctors had of saving her.

When she arrived at the hospital, Giese couldn't talk, sit or stand and fell in and out of consciousness—she also needed to be intubated to help her breathe. "She was critically ill," Willoughby recalls, "and looked as if she might die within the day."

In addition to inducing the coma, doctors also gave her the antivirals ribavarin and amantadine. They tapered off the anesthetics after about a week, when tests showed that Giese's immune system was battling the virus. For about six months after awakening from the coma, physicians also gave her a compound called tetrahydrobiopterin that is chemically similar to the B-complex vitamin folic acid, which may have improved her speech and ability to eat, Willoughby says.

He notes that physicians gave her the supplement after tests showed that she had a deficiency of the compound, which is known to boost production of serotonin and dopamine neurotransmitters needed to perform motor, speech and other routine bodily functions.

Remarkably, Giese survived. She recovered most of her cognitive functions within a few months, and other skills within a year, Willoughby says. She got her driver's license and is now a sophomore at Marian University in Fond du Lac, where she is majoring in biology. There are lingering signs of her illness: Giese, once an avid athlete, says she now lists to one side when she runs and walks and no longer plays volleyball, basketball and softball as she once did. She also speaks more slowly and sometimes not as clearly as before her illness, but Willoughby says these effects may fade over time.

Giese is "pretty much normal," says Willoughby, an associate professor of pediatrics at the Medical College of Wisconsin in Milwaukee. "She continues to get better, counter to conventional medical thinking."

Rabies has an incubation period of two weeks to three months and kills within a week of the symptoms showing up. The vaccine series and other immune therapies are useless at this point and may even speed up and increase the severity of the symptoms. Usually, patients are made as comfortable as possible in the hospital or, in countries without sophisticated health care, sent home to die an agonizing death.

Antiviral drugs and immune therapies including steroids, disease-fighting interferon-alpha and poly IC (which stimulates the body's own production of interferon-alpha) have been tried, but none have been shown to be lifesaving on their own, Willoughby says.

Over the past four years, the Milwaukee protocol to differing degrees has been used a dozen times, but until now Giese was the sole survivor. Exactly why she lived—and the others died—is still a mystery.

In a 2005 report on her case in The New England Journal of Medicine, Willoughby speculated that she may have been infected with a rare, weakened version of the virus. Today, he chalks Giese's survival up to aggressive intensive care, the decision to sedate her "and 10 percent sheer luck." Which element of that combination made the difference, and whether the antivirals she was given helped save her is unknown.

"In all honesty, we were probably just pretty lucky," he says. Only another survivor, and then animal and clinical trials, will show if the therapy works, and why, he says. The U.S. Centers for Disease Control and Prevention (CDC) plans to test the protocol on rabies-infected ferrets; Thai and Canadian doctors, who unsuccessfully treated a 33-year-old man with rabies with the Milwaukee protocol, recommended in the Journal of NeuroVirology two years ago that physicians exercise "caution" in using the treatment, because it is too expensive and lacks " a clear scientific rationale." Willoughby says it cost about $800,000 to treat Giese.

Rabies is 100 percent preventable with vaccinations if patients receive them before the onset of symptoms, including hallucinations, delirium, muscle spasms, paralysis and hydrophobia. Yet an estimated 55,000 people, mostly in Asia and Africa, die from it annually because of misdiagnosis or because the illness is not recognized until it has taken hold, according to the journal Neurologic Clinics. Often, patients dismiss the potential seriousness of bites, cannot afford follow-up medical treatment or, in some situations, are unaware they've been bitten, as was the case of a 13-year-old Connecticut girl who died of rabies in 1995.

Vaccine shortages as one manufacturer, Bridgewater, N.J.–based sanofi–aventis, upgrades its factory to meet U.S. Food and Drug Administration requirements, and chronic shortfalls of immunoglobulin also play a role in the fatalities. The vaccine-immunoglobulin regimen costs $1,200 to $2,000 in industrialized nations and $100 to $300 in developing countries—an out-of-reach sum for many people, Willoughby says.

Though it's promising that Gomez is still alive, "The hope that the outcome will necessarily be the same as with Jeanna, particularly in a developing country, is expecting a bit much," laments Charles Rupprecht, chief of the CDC's Rabies Program

Willoughby acknowledges that even if Giese's success is reproducible—and the Milwaukee protocol perfected—it likely will only be available for use in 10 percent of cases, because of limited medical facilities in developing countries.

"Re-creating that in a place stricken with poverty, you get into ethical issues of whether we should do this when we should be about prevention; and does that society have the ability to rehabilitate a patient who may survive but with severe [side effects]?" Rupprecht says. "Jeanna created several ethical issues for all of us to deal with this bug."

Giese says that the fourth-year anniversary of her illness has brought up some bitter memories that she'll probably never shake, but she's glad to be alive—and doing as well as she is.

"It takes some getting used to, but I've kind of come to terms with the fact that I'm the only…[survivor]," she says. "At 15, I never would have thought that anything like this would ever happen, and that I lived is just amazing."

An animal lover who owns a dog, two rabbits and six birds, she hopes to one day open a sanctuary in Fond du Lac for endangered animals, including "big predators like lions and tigers and wolves," and maybe even bats, too.

"I'm not scared of them at all," Giese says of bats. "I'm more passionate about animals than I was before. Animals are my happiness and reason for living."